The overall objective of the proposed research is to better define the role of mechanical interactions between the left ventricle (LV) and systemic arterial system (SA). This objective has been divided into four subgoals: 1) identification of the properties of the aortic-valve/aortic-bulb region as the mechanical coupler between LV and SA; 2) identification of LV pump properties that account for behavior over a wide range of flow states and, particularly, that behavior that marks the transition between contracted and relaxed myocardium; 3) specification of how the multiple LV pump properties change with enhancement of the myocardial inotropic state; 4) characterization of the nonlinear aspects of LV/SA interaction by examining the sensitivity of this system when there has been separate changes in vasoactive and inotropic states. An anesthetized, instrumented, open-chest canine experimental preparation will be used. This preparation will be used without and with right-heart bypass in the different experiments. Righ-heart bypass will be employed to achieve a great degree of physiologic stability in those experiments that require long-term stability and it will not be used where a high degree of physiologic vitality is required. Mechanical devices that will be used to impose experimental perturbations include a clamping device for aortic occlusion and a servo-controlled piston diaphragm device to cause reduced LV pressure development during ejection. These perturbations will be imposed and removed in a variety of patterns to create and experimental design where LV pump properties are evaluated from beats with greatly different beat histories. All responses will be analyzed using the digital compute for comparing predictions from competing models with actual data. The results of these analyses will provide a deeper understanding of: 1) how to characterize LV and SA function; 2) the means by which LV/SA function changes when there has been a change in either the LV or SA or both; 3) the functional considerations that must be used in the design of therapy to modify malfunction brought about by cardiovascular disease.